The Study

We have discovered a new molecular ‘switch’ that controls the properties of neurons in response to changes in the activity of their neural network. Our findings suggest that the ‘hardware’ in our brain is tuneable and could have implications that go far beyond basic neuroscience. Computers are often used as a metaphor for the brain, with logic boards and microprocessors representing neural circuits and neurons, respectively. While this analogy has served neuroscience well in the past, it is far from correct. The brain is a highly dynamic, self-organising system, in which internal and external influences continuously shape information processing ‘hardware’ by mechanisms not yet understood, and in a way not achieved by computers. We have shed light on this problem by discovering that some neurons in the cerebral cortex can adapt their properties in response to changes in network activity – such as those observed during learning of a motor task. We studied two apparently different classes of fast-spiking interneurons, only to discover that they were actually looking at the same piece of ‘hardware’ which had the ability to oscillate between two different ground states. We have also identified the molecular factor responsible for tuning the properties of these cells, a transcription factor – a protein able to influence gene expression – known as Er81.

Hippocampal place cells, which create an internal map during novel exploration, are getting ‘replayed’ during sleep

Background

Fast-spiking interneurons are part of a general class of neurons whose primary role is regulating the activity of the principal cells of the cerebral cortex, known as pyramidal cells. The cerebral cortex is outer layer of the brain and is associated with cognition, language and memory. Our research over the past five years has largely focussed on the analysis of the mechanisms controlling the generation, migration and wiring of cortical interneurons. We previously found that neurons generated in the medial ganglionic eminence (MGE), a transitory brain structure, express the transcription factor known as Er81. Because Fast-spiking interneurons derive from the MGE, we investigated whether Er81 is expressed in this population of interneurons.

Future Directions

Understanding the dynamic mechanisms that lead to the emergence of brain functions through the development and continuous remodelling of neural circuits, and the constraints that disease and ageing impose to this multi-modal plasticity has important implications that go beyond fundamental neuroscience, from education policies to brain repair. Our study demonstrates the tremendous plasticity of the brain, and how this relates to fundamental processes such as learning. Understanding the mechanisms that regulate this plasticity, and why it tends to dissipate when we age, has enormous implications that go beyond fundamental neuroscience, from informing education policies to developing new therapies for neurological disorders such as epilepsy.